Dystrophic neurites in TgCRND8 and Tg2576 mice mimic human pathological brain aging

The morphology and neurochemistry of β-amyloid (Aβ) plaque-associated dystrophic neurites present in TgCRND8 and Tg2576 mice was demonstrated to be strikingly similar to that observed in pathologically aged human cases, but not in Alzheimer's disease (AD) cases. Specifically, pathologically aged cases and both transgenic mouse lines exhibited α-internexin- and neurofilament-triplet-labelled ring- and bulb-like dystrophic neurites, but no classical hyperphosphorylated-tau dystrophic neurite pathology. In contrast, AD cases demonstrated abundant classical hyperphosphorylated-tau-labelled dystrophic neurites, but no neurofilament-triplet-labelled ring-like dystrophic neurites. Importantly, quantitation demonstrated that the Aβ plaques in TgCRND8 mice were highly axonopathic, and localised displacement or clipping of apical dendrite segments was also associated with Aβ plaques in both transgenic mouse models. These results suggest that neuronal pathology in these mice represent an accurate and valuable model for understanding, and developing treatments for, the early brain changes of AD.